2-Thiophenecarboxaldehyde, 5-chloro- → HCID 9949225, compound

Temperature

40 °C

A solution of 5-chlorothiophene-2-carbaldehyde (240 μL, 111 μmol, 463 mM in 1,2-dichloroethane) was added to a solution of 4-amino-2-nitrophenylcarbamic acid ethyl ester (240 μL, 111 μmol, 463 mM in 1,2-dichloroethane). Sodium triacetoxyborohydride (118 mg, 555 μmol) was added, and the resulting mixture was stirred for 3.5 hours at 40° C. The mixture was allowed to cool to ambient temperature, and water (100 μL) was added. The mixture was filtered through silica gel (500 mg) and the column was washed with 1,2-dichloroethane (3 mL). The combined organic phases were evaporated to dryness in vacuo. The resulting solid was dissolved in ethanol (3 mL). Iron (19 mg) was added to one-third of the resulting solution (1 mL), followed by an aqueous solution of hydrochloric acid (96 μL, 6M). The resulting mixture was placed in an ultrasonic bath for 10 minutes. Then, saturated aqueous sodium bicarbonate solution (2 mL) was added. The mixture was extracted with ethyl acetate (3 mL). The organic phase was washed with water (3 mL) and brine (3 mL), dried over magnesium sulphate, filtered, and evaporated to dryness in vacuo. The resulting product was dissolved in 190 μL dimethylsulfoxide and subjected to preparative LC-MS purification. The resulting solution was evaporated to dryness in vacuo. Yield (6.8 mg, 56%). LC-MS (m/z) (M+H)+ 326.1 RT=1.90 (UV, ELSD) 92%, 99%.

1. temperatureto cool to ambient temperature
2. filtrationThe mixture was filtered through silica gel (500 mg)
3. washthe column was washed with 1,2-dichloroethane (3 mL)
4. customThe combined organic phases were evaporated to dryness in vacuo
5. dissolutionThe resulting solid was dissolved in ethanol (3 mL)
6. additionIron (19 mg) was added to one-third of the resulting solution (1 mL)
7. waitThe resulting mixture was placed in an ultrasonic bath for 10 minutes
8. additionThen, saturated aqueous sodium bicarbonate solution (2 mL) was added
9. extractionThe mixture was extracted with ethyl acetate (3 mL)
10. washThe organic phase was washed with water (3 mL) and brine (3 mL)
11. dry with materialdried over magnesium sulphate
12. filtrationfiltered
13. customevaporated to dryness in vacuo
14. dissolutionThe resulting product was dissolved in 190 μL dimethylsulfoxide
15. customsubjected to preparative LC-MS purification
16. customThe resulting solution was evaporated to dryness in vacuo
17. customYield (6.8 mg, 56%)
18. custom326.1 RT=1.90 (UV, ELSD) 92%, 99%

ORD record

ord-fa268629e26c41298b3aaecf7d583e28

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07368472B2